Our goal is to understand how growth hormone action in target cells in regulated. We believe that the availability of growth hormone binding sites at the exterior surface of the cell is directly relatable to cellular responsiveness in the hepatocyte. We plan to assay for changes in receptor affinity and availability and correlate these with the ability of growth hormone to stimulate protein synthesis and protein phosphorylation. An affinity crosslinking methodology will be developed to covalently couple growth hormone to its hepatic receptor. The structure of the receptor will then be characterized. Development of such methodology will also permit the definition of a structural basis from which to understand changes in receptor binding and cellular sensitivity.